All-In Podcast
Bryan Johnson: acabo de tomar la dosis más potente de DMT del mundo… así fue la experiencia
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TL;DR
Resumen de investigación
▶ Marco de longevidad y decisión de probar 5-MeO-DMT
Johnson cuenta que tomó 5-MeO-DMT unos dos días antes y que todavía está aprendiendo a describir la experiencia. Explica que su proyecto de longevidad empezó hace cinco años con una revisión de la evidencia científica para priorizar intervenciones según su evidencia y tamaño de efecto: ejercicio, nutrición y sueño, además de oxígeno hiperbárico, sauna, rapamicina y metformina. Los psicodélicos no estaban inicialmente en su radar como terapias de rejuvenecimiento; tras encontrar evidencia preclínica en ratones sobre psilocibina, realizó un experimento que describe como muy cuantificado, con tres dosis de 25 mg. Afirma que consideran que podría ser una terapia de longevidad y anticipa los datos antes de mencionar que luego probó 5-MeO.
▶ La experiencia subjetiva con 5-MeO-DMT
Johnson dice que la experiencia es difícil de explicar y la describe como contacto con «conciencia e inteligencia» en estado puro, una escala que considera casi imposible de transmitir. Relata que la sustancia lo llevó fuera de su experiencia ordinaria con rapidez y que fue poco visual, a diferencia de lo que asocia con DMT. Dice que sintió que podía entrar en pánico ante la impresión de que la existencia lo despedazaría, o rendirse; al abandonar apego, deseo, ego y control, experimentó dicha y euforia. La califica como la experiencia humana más intensa que ha vivido, incluso frente a logros, matrimonio, tener un hijo o superar dificultades. Señala que al principio no sabía qué ocurría y luego estuvo muy consciente, aunque sin el monólogo interno habitual.
▶ Red cerebral, plasticidad y la hipótesis de rejuvenecimiento
Johnson explica el modo por defecto como el sistema que, según su descripción, construye el yo y el ego y sostiene la rumiación. Opina que con la edad se forman patrones más rígidos que estrechan la experiencia de la realidad. Describe la psilocibina como una intervención que debilita esos patrones y reorganiza la actividad cerebral: usa la metáfora de rutas aéreas entre aeropuertos y dice que las mediciones de Kernel mostraron conexiones nuevas y patrones antiguos más silenciosos. El entrevistador relaciona esos cambios y la neuroplasticidad con posibles cambios en trauma y ansiedad; Johnson responde que esos efectos de psilocibina están documentados. La conversación pasa a preguntar cómo conecta esa evidencia con la longevidad.
▶ Resultados que atribuye a la psilocibina y efectos personales
Johnson dice que datos en ratones mostraron efectos de la psilocibina y reducción de inflamación, algo que consideró relevante porque asocia la inflamación con terapias de longevidad. Relata una observación personal que presenta como primera en humanos: después de la psilocibina, su glucosa sanguínea pasó de estar en el percentil 99,5 al 99,9, y también observó cambios en su microbioma; interpreta que fue un «reinicio» metabólico más amplio que un efecto directo sobre la glucosa como el de la metformina. A partir de esos resultados consideró que 5-MeO-DMT podría compartir características, aunque menciona que la evidencia era animal. Afirma que 5-MeO-DMT le pareció mucho más fuerte que la psilocibina para reducir la actividad del modo por defecto. Cuenta que después se sintió más infantil y emocionado por las actividades cotidianas, que se rio en un sueño —algo que dice no recordar haber hecho antes— y que una discusión con su pareja se resolvió sin necesidad de defenderse o escalarla. También dice sentirse más gracioso y renovado. Antes había probado psicodélicos sobre todo durante una etapa de reconstrucción personal tras vender Nootrobox, divorciarse y dejar la Iglesia mormona; describe su experiencia con ketamina y mediciones de Kernel como transitoria y mucho menor que la de 5-MeO.
▶ Mediciones pendientes y cautela ante los riesgos
Johnson enumera las mediciones que hicieron alrededor de 5-MeO-DMT: resonancia estructural y funcional, Kernel y EEG en tiempo real. Dice que aún no tienen resultados para compartir y que buscaron observar el cerebro desde distintas modalidades, como flujo sanguíneo, estructura, señales moleculares y patrones de ondas, porque le parece difícil rejuvenecerlo. Sobre psilocibina, el entrevistador refiere una restauración marcada de patrones cerebrales juveniles. Johnson expresa gran interés en los psicodélicos, pero insiste en que son potentes y requieren un profesional con licencia, preparación y cautela; no los recomienda indiscriminadamente. El entrevistador plantea el riesgo de psicosis permanente o estados esquizofrénicos en personas predispuestas. Johnson está de acuerdo en que algunas personas sufren consecuencias y malos viajes que las dejan afectadas. Considera que el uso no cuantificado, sin supervisión y con un set y setting inadecuados puede contribuir al riesgo, aunque reconoce que este persiste y que algunas personas no son candidatas apropiadas. Opina que protocolos rigurosos podrían reducir riesgos, sin afirmar que puedan eliminarlos.
▶ Efectos duraderos, cambios de vida y riesgo para terceros
Johnson compara subjetivamente su experiencia con mejorar la dieta, hacer ejercicio, dormir bien, usar sauna y oxígeno hiperbárico; dice que 5-MeO-DMT fue más eficaz para el «reinicio» personal, pero no sabe cuánto durará ni si volverá a ser como antes en 30 o 60 días o necesitará repetirlo. El entrevistador señala que algunas personas, tras psicodélicos intensos como ayahuasca, dejan empresas, familias o parejas porque cambia su perspectiva, y que inversores, empleados y familiares pueden verse perjudicados. Johnson confirma que ha oído de inversores que incluyen en documentos de inversión restricciones para que fundadores no usen psicodélicos durante la vida de la empresa, por el riesgo de que se alejen y dejen al equipo sin apoyo. Distingue esos usos sociales o en retiros, que a su juicio suelen no estar cuantificados ni controlados, de un enfoque más riguroso. En su caso, dice que volvió más motivado a su trabajo y no quiere irse a vivir al bosque, aunque admite que el cambio de perspectiva puede ser dramático y difícil de ignorar.
▶ Identidad, flexibilidad y responsabilidades personales
El entrevistador pregunta si una persona sigue siendo la misma cuando una sustancia puede modificar en horas las conexiones que reflejan sus experiencias. Johnson coincide en que la reconstrucción le parece muy profunda y compara su alcance con una experiencia cercana a la muerte; ambos consideran que pueden cambiar los valores, incluso respecto a religión, familia, hijos o pareja, y plantean si esos cambios son correctos. Johnson sugiere que, en un mundo donde la innovación impulsada por la IA acelera el cambio, la capacidad de adaptación podría convertir esa reestructuración en una ventaja, pese al riesgo de que cambien las prioridades. A preguntas hipotéticas, dice que consideraría un implante neural y una intervención transgénica, y responde que no ve un límite a lo que probaría. Atribuye su interés por la novedad y la exploración, quizá, a una reacción frente a una infancia en un entorno religioso estructurado; dice desconfiar de su propia construcción de la realidad y tener 188 sesgos crónicos, como todos los humanos. Sobre las responsabilidades, afirma que ser padre de tres hijos sigue siendo central para su identidad. Dice que su entorno lo anima a experimentar y que su pareja Kate asumía riesgos ante la posibilidad de que algo saliera mal o cambiara su perspectiva; acepta que el apoyo también puede entenderse como permitir esos riesgos.
▶ Terapias futuras: mitocondrias, genes y organoides
Al hablar de otras modalidades de longevidad, Johnson dice que las terapias celulares y génicas están en desarrollo y que, en su opinión, ya han recorrido las intervenciones disponibles actualmente. Le interesa el rejuvenecimiento o aumento mitocondrial y comenta un artículo sobre mitocondrias recubiertas con una envoltura similar a la de glóbulos rojos para facilitar su transporte a las células y reducir el ataque inmunitario. Dice tener una terapia mitocondrial prevista con una empresa externa: espera hacerse una extracción de sangre en una o dos semanas para que amplíen las mitocondrias y luego recibirlas. Reconoce que el enfoque es exploratorio y que no saben si funcionará; el entrevistador señala que se encuentra en fase dos. Conversan sobre medir el resultado con sprints, una propuesta que Johnson considera buena, aunque dice que no hace sprints y bromea con que su edad aproximada es 74 años. También discuten terapias con FoxO3 y células madre mesenquimales: Johnson califica como notable un resultado que, según describen, rejuveneció más del 50% de los tejidos, y dice que contactó al profesor asociado al trabajo para explorar su replicación. Le gustaría construir el sistema, pero estima que llevaría dos años. Además, dice que ya tienen organoides de corazón, hígado y pulmones derivados de sus células iPS, y que planean probar moléculas en ellos; aún no han hecho la primera prueba y el concepto está por validar.
▶ Factores de Yamanaka, inversión en NewLimit y posibles efectos sociales
Johnson dice ser inversor en NewLimit y que la empresa ha avanzado en la búsqueda computacional de factores de rejuvenecimiento más rápido de lo previsto. El entrevistador señala que una dosis excesiva de factores de Yamanaka puede hacer que una célula se vuelva cancerosa y forme un tumor. Johnson plantea como teoría que interruptores celulares ajusten la síntesis de proteínas según la expresión génica; el entrevistador coincide en que el control debe ser preciso. El entrevistador presenta estas tecnologías como especialmente transformadoras, junto con la IA, y ambos especulan que los GLP-1 podrían verse como una primera gran ola, seguida quizá por NewLimit u otras terapias plasmáticas de FoxO3 con cambios importantes en la vida real. Hablan de que una mayor longevidad y abundancia podrían repercutir en la sociedad. Johnson sostiene que la mala salud contribuye al malestar y a dificultades psicológicas; menciona, atribuyéndolo a la conversación, que el 84% tiene trastorno metabólico y más del 40% tiene obesidad, además de problemas de sueño, uso del teléfono y salud mental. Opina que mejorar la salud podría aumentar la disposición de las personas y comunidades a afrontar tareas difíciles. El entrevistador pregunta cómo encajan los psicodélicos en esa cartera de intervenciones.
▶ Posible papel complementario de los psicodélicos y cierre
Ante la pregunta sobre cómo integrar las intervenciones, Johnson dice no recordar si el estudio de FoxO3 mostró rejuvenecimiento cerebral; ambos señalan que el cerebro es complejo y que regenerar neuronas de manera incorrecta podría tener consecuencias desconocidas. Johnson plantea que psilocibina y 5-MeO-DMT quizá no mejoren funciones corporales básicas, pero podrían destacar por el efecto sobre la disposición ante la realidad. Dice que teme perder con la edad una actitud juvenil de «puedo hacer cualquier cosa» y que, en su caso, los psicodélicos le han devuelto esa sensación. Describe la experiencia como si hubiera recibido 30 o 40 años de rejuvenecimiento psicológico y aclara que no obtiene eso de la sauna, la alimentación o el sueño. El entrevistador los considera únicos. Cierran con una broma sobre acostarse tarde, beber alcohol y comer carbohidratos frente a seguir una rutina para dormir; agradecen la conversación y despiden a Johnson.
Transcripción completa
[00:30] CEOs and VCs have in common? They sleep on the pod by Eight Sleep. It's become tech's favorite way to sleep and for good reason. A cover that goes on any mattress cools it down to 55° and uses AI to adjust your temperature all night. Up to 34% more deep sleep. No wearable needed. Go to eightsleep.com/allin and use code allin for up to $350 off your pod purchase today. Before we get into your experience, why did you choose to do it? Two things. One, mostly as a longevity experiment.
[01:00] So, when we when I started this project 5 years ago, the the approach we had was go through all of the scientific evidence ever published on health and longevity. Try to find the interventions that have the best evidence. And for effect size and we just went down the list from top performing on down. So, of course you start with exercise, nutrition, you know, sleep. And you work your way down to things like hyperbaric oxygen therapy and sauna and then rapamycin metformin. And so, we never actually had on our
[01:30] radar psychedelics. They were always either an ancient medicine you know, being used in in ritualistic practices or being pointed at things like depression and anxiety and in certain trials. But it was never understood as a rejuvenation protocol, something that was for anti-aging. And so, we found a preclinical evidence in mice on psilocybin. We thought, that's interesting. And so, we did the world's most studied the most quantified experiment doing psilocybin. Three doses at 25 mg of psilocybin. Which is a pretty high
[02:00] doses. It's yeah, it's a clinical dose, a very very close to a hero dose. And we found that we think it's a a longevity therapy. Let's get to that data in a minute. But then you decided to try 5-MeO this weekend. Yes. Walk me through the experience cuz you televised the whole thing. It was live streamed. You looked amazingly calm going into it and going through the process. Walk us through your experience. Yeah, I think those who have done 5-MeO
[02:30] would probably relate with me that it feels like an impossible task to explain what it's like. So, that caveat said, I'll I'll give it a go. I'm stunned. Absolutely floored, speechless. You you basically experience raw consciousness and raw intelligence. It's this So, whatever when I say these words, take these words that I convey to you, take that idea, multiply it by a
[03:01] thousand, and then move out infinite depth, infinite width width and then dimensions. And like that gives you kind of like a rough map of like the size and space that you deal with. And it was incredibly hard cuz you you get blasted into this space that is so foreign. You don't even know what's happening. >> It happens very quickly. Like you you inhale it. I did 9 mg of intramuscular and then 7 18 of vaporized. And it takes you within 10
[03:31] seconds. You're just out you're out. And so, but what happens is you you get in that space and then Visual changes everything? >> Very very little visual. Like you see that on DMT it's a very visual. You'll meet the you know, like the elves or whatever else. This is not a visual experience. But you you get in this world and you lock in to basically you either panic because you feel like the gates of hell are going to open. That the
[04:01] the stream of existence is going to just tear you to shreds. It's going to shard you. And if you give up >> Like break your brain. Yeah, it's if you feel like it's going to like threaten your sanity. Like is it going to chop you up into little pieces? And so, in that moment you have to say, do I try to wrestle this and I I need to just like wait it out until it's over or you just relent and you say yes. And you have to in that moment you have to say yes so thoroughly. You have to
[04:32] release all attachment, all preconditions, all want, all desire. You have to release self, ego, control. You just have to just relent entirely. And then when you do that, it opened up this unimaginable bliss and euphoria. And like I again, this is like a V1 of trying to explain this. But if I list out the the most dynamic experiences I've had as a human,
[05:04] you know, uh like certain accomplishments or getting married or having a child or overcoming a difficulty or you know, state your list things. This is without question the most dynamic experience I've ever experienced as a human. Does the internal chatter, the internal monologue of the ego turn off? Does. So, you can't hear yourself speaking. How do you rationalize what's going on if you don't have a dialogue going on? It's this visceral feeling. Like you're you're hyper aware of what's
[05:35] happening. It's not like you you block out in the first like when you take a very high dose, you don't really know what's happening the first few minutes, but then you kind of come to and you're hyper aware of everything. It's not visual, but it's this um you're in the depths of existence. [snorts] Like this It's just the most majestic experience
[06:05] achievable by a human by by intelligent life. I just can't imagine anything more miraculous. You've studied the biology, the biochemistry. What goes on in the brain as this molecule hits your neurons? >> Yeah, I mean like it I mean one, it completely dissolves your default mode network. >> Describe what that is. So, like um it's this is the engine that constructs self and ego. And so, as you ruminate, you know, like you're going through
[06:35] Thinking through your day. What's next? How am I feeling? What should I be doing right now? Yeah, it's like constant conversation. >> I feel bad about myself? Do I feel, you know, like I am I shy? Am I like do I feel bad about whatever? Like you're doing this rumination stuff. Kids don't have this rumination loop. Their their default mode network is is quiet. And as you age, you basically build up this default mode network into more stiffer patterns. And so, as you age, your experience of reality becomes increasingly narrow. You have these big ruts that form. And so, you can just see
[07:05] people in their patterns like how open a child is to say like very random things that as adults you're just very you're shut in. Like when I did psilocybin, one of the reasons why we did it is because it does have this effect where it dampens the default mode network. And then we could pick this up with Kernel, the brain interface. You can see how the default mode network weakens. Like so basically I think of the brain like a globe with airports scattered about. And you have certain traffic patterns like New York to London. You have a certain number of flights every day. That's like a very strong connection. But New York
[07:35] to you know, some small town in in Arkansas has a very low traffic map. And so, when you do something like psilocybin, it basically takes the airports, picks them up and then repositions them in the world. So, they're just all scrambled. So, that the traffic patterns aren't the same. And then over time >> don't physically move, but the activity shifts around. >> Exactly. >> Right. The neurons are a little bit more random than they normally would be, which arguably drives neuroplasticity, causes those neurons to reach out for
[08:06] new connections. And when new connections are made, new behaviors, new ways of thinking emerge. >> Exactly >> Coming out of these therapeutics. Is that a fair way to describe it? >> Exactly right. So, you look at my brain on psilocybin from Kernel, you see my patterns before like the New York to London connection. You see my brain afterwards and it's exactly what you said. New patterns are emergent. The old ones have have have quieted down. It's like a new map of connectivity. And so, we saw that happen and that does generate a lot of neuroplasticity. >> And obviously this neuroplasticity rewiring these connections in the brain
[08:37] is what allows trauma victims or folks that have a certain wiring that they keep repeating in their brain which causes the trauma and the anxiety in their lives to get rewired and then that trauma and that anxiety feels like it dissolves or melts away. Is that a fair way to describe it? >> Yeah. And so, this is this has been documented in psilocybin. It's kind of well understood. How did you connect that psilocybin data to an effort in longevity or was this just like a random idea, let's try it out? >> Yeah, well so we we we saw some mouse
[09:07] data that it had these effects. It also showed reduced inflammation. So, we said like this is interesting cuz most longevity therapies do something with inflammation, right? Like inflammation is the killer. So, if you can lower inflammation, it's a very good sign. If you can do something that makes the brain more youthful and takes down those those big ruts, that's also useful. What we found in psilocybin though is that it had we found a first in human observation. It had this this metabolic reset in the brain where my blood
[09:37] glucose before this was in the top 99.5% of all the population. Okay. After, it went to the top 99.9%. Like to move my blood glucose from that level is very very hard. And but it basically like not like metformin where you're doing something on blood glucose. This just had a reset across the body. Also changed my microbiome. So, we saw full-on effects. So, then we said, "Okay, if that had that consequence, 5-MeO may have some similar characteristics." And so, >> one had done this in 5-MeO before. Exactly. So, there's like there's
[10:08] potential There's actually some animal evidence. But, it's the these the similar dynamics of like can you take the brain and can you basically like smooth out the barnacles that accumulate? And 5-MeO-DMT compared to psilocybin like just absolutely like blasted clean my default mode network. It felt like psilocybin dampens it. It like it softens it, but this thing just annihilated my default mode >> Turned it off completely. Yeah. It just It just doesn't run the same way. Like
[10:38] for an example like uh this morning I woke up uh catching myself laughing in a dream. I have not laughed in a dream. I don't I don't even know when I've ever laughed in a dream. But, that is I after I woke up I was like, "That's really weird." Like I don't remember laughing. I looked it up and like that is a characteristic of a thing of a child. >> Right. And so, you are restored to this childlike state. And I mean the past couple days uh I have felt childlike. You know, yesterday morning I felt that you know, that emergent excitement, the bubbling
[11:09] of like today is so exciting. I'm going to do new things. I'm going to have new experiences um that you're just excited about all things. I haven't felt that I don't even know when you know, for so many years. So, like it really was um profound on every layer. And I feel like I'm stumbling through it cuz I don't even know how to talk about it. During the day, you're hanging out, you're walking around, is your brain having the same normal chatter that it did before or do you think that there's a persistent change in that default mode network? Yeah, definitely change. Like with I was
[11:40] I was with my partner Kate yesterday and we um I did something that made her upset. And so, like in that situation, you know, like when when couples are in that moment, you have like this negotiation. How do I sort this? And it all just became so clear to me like when children have a fight, you have it out and then it's just like done. Yeah. And you move on. But, then adults take that and they like package it up and like then they weaponize it and be like, "I got something on you."
[12:10] And I'm like move it. I'm going to move the chess pieces and like try to leverage this and and um Or they store it up like a snake in one of those things that pops out all the things later, you know? >> [laughter] >> It's like package it all up. Exactly. And so, like we had this and I I just felt um absolutely like no need to escalate or to defend or to like it was just easy. >> Easy. And um it was a breakthrough in our relationship where I was able to communicate with her in a way. And so, it's like laughing in my sleep. It's how I deal with my
[12:40] partner. When I walk around, I just feel so much I uh I feel so much more funny. You know, like my ability to make quips that are just immediate. Uh you know, like So, yeah. I just feel renewed as a person in a way that I just really didn't imagine. Have you tried hallucinogenics before you started your longevity path a couple of years ago? >> Yeah. And did you do that recreationally or therapeutically? It was mostly therapeutic in that I I'd sold my
[13:10] company Nootrobox. I got a divorce. I left the Mormon church. And I was trying to remap like what is life, who am I, what do I do? So, I was in that rebuilding stage where I just dabbled of like you know, I did I did ketamine at Kernel. So, one one of our first studies at Kernel is we said ketamine was a up-and-coming therapy for depression. And we posed the question, "What happens when you do ketamine?" And so, we did the world's most extensive measurement of ketamine with Kernel before, during, and after. And so, that was interesting like and it had some kind of you know,
[13:40] transient effect, but that's like a a like a little league relative to 5-MeO. And so, as you've gone through this, maybe share a little bit of the MRI data that you're gathering and the other data mapping neurological effects. Yeah. And tell us a little bit about what you've learned. So far, nothing. Uh I have my subjective experience to share, but we we have a structural brain MRI. We have a functional brain MRI. We did Kernel, which is like an optical interface. And then I did real-time EEG capture. And we should just talk about I
[14:11] think it's important structural. You can see the the physical brain. Functional, you can see the activity in the brain. So, neurons firing and neurons that are not firing, Yes. Yeah. And then electrical actions that are measured by a electrical device. >> Yes. So, we basically like wanted cuz the brain is very So, we've had a lot of success rejuvenating my heart and my lungs and muscle and body fat. But, rejuvenating the brain is very hard. >> Right. And so, we This is why this is so
[14:41] such a promising therapy. So, we wanted to look at the brain through every modality possible. We wanted to look at blood flow, structural, molecular, you know, the wave pattern form. So, it's a it's a very high fidelity quantification. And so, we'll see what the data comes out. Um I'm very excited. Yeah. >> this on psilocybin as well, right? You mapped the brain over time. What did you learn there? Dramatic uh restoration of youthful brain patterns. Yeah, right. Yeah. And what comes after 5-MeO?
[15:11] >> [laughter] >> You know, I I mean, how far do you take this? >> Yeah. Honestly, um I am so encouraged by psychedelics. I you know, like in in in the community where I hang out, psychedelics have always been understood as you know, it's like a retreat or it's like a a ritual you go to like do various explorations. But, never in the world of longevity. It's never been understood as that thing. And now after seeing the data,
[15:41] now I um And of course, you have to be very careful when talking about psychedelics because they're extremely powerful. It's not like go out and do them everybody, right? It's like it needs to be done properly with a licensed professional. It needs to be done carefully. The person needs to be in the right state. Like it is not to be taken lightly. But, I am uh more interested than ever in psychedelic compounds. I mean, they're just uniquely powerful. There is some arguments to be made that psychedelics can induce permanent psychoses, >> Yeah.
[16:11] cause functional changes and drive some people that might be predisposed into schizophrenic states. >> That's right. How did you get over those risks? Because for a lot of people, that would turn them off to trying psychedelics. >> Yes. And it's not a non-zero percentage of people that suffer these consequences. >> Yeah. I agree. And and also people who have really bad trips that leave them scarred. So, it's it really is. And I think in in part of it is um what could be contributing to this is uh people who for example who have tried
[16:41] uh magic mushrooms, you know, it's in a social situation. Someone's got a bag. You pull out the mushrooms. It's like, "Yeah, like weighs blank." And they pop it in. But, they have no idea what kind of mushroom strain they're eating. They don't know what the dose of psilocybin is. Uh so, it's like unquantified, unsupervised, wrong set and setting. And so, much of it I think you can The the risk persists, but I don't think we we've approached psychedelics with the appropriate rigor that we should to make it safe. And so, it's not to say that we can solve for the safety issues for all people. Some people just may not be the
[17:11] appropriate candidate for it. But, I think if we do create a safety structure around it, they could deliver the benefits people want uh without you know, with less of the risk. But, definitely I agree with you like it's again it it deserves all the caution in the world. You can get like neurogenic, neuroplasticity, trauma resolution. I mean, what is the way that this is going to be allowed to become call it a medical therapeutic that can be more broadly trialed and then eventually figure out how to bring
[17:42] it to people without it being carrying all the risks and burdens that it does today? >> I mean, if I just subjectively compare my experience with 5-MeO to having a better diet and exercising every day and uh sleeping well and doing the sauna and doing hyperbaric oxygen therapy, this was more efficacious than all of them in terms of the reset of me as a human. It it just is incomparable. And I guess I'm I'm really left pondering. I mean,
[18:13] like for this molecule to have such a gigantic impact. Now, like how long will it last? What's the decay curve like? You know, will I find I I become the former Brian within 30 days, 60 days? Do I have to repeat the cycle? And I don't know. But, it really is you know, you When you sleep well, you feel great. You exercise, great. But, like nothing like what 5-MeO did in terms of of like the reset of me as a human. So, let's just talk about the consequences outside of the physiological, which is life. Yeah. There lots of stories and friends that I have that and
[18:45] people that I know that have tried a heavy psychedelic like an ayahuasca or something. They were the CEO of a company and then they quit their company and they go off to the jungle, leave their family, divorce their their partner, um make such dramatic life changes because their perspective has been shifted so much that they reevaluate what matters in life to such a degree that they give up a lot of the things that mattered before. >> Yeah. In the wake of that, there are people that
[19:15] feel they're a victim of that behavioral shift. The investors in the company, the employees, the family members, et cetera. >> Yeah. Can you just talk a little bit about those broad risks? Because we've seen it and I'm and I don't know if you've seen the same. But, friends that have kind of like said, "I have this new perspective. I'm giving up my life." I've seen the same thing. And I um one investor told me that he even put it in the deal docs that you know, if we invest, you're not going to do these psychedelics. Cuz they they wanted to minimize the the risk
[19:45] profile. It's a thing. In your deal in an investment in you? No, I just spoke cuz because I've been doing this. Uh uh People bring this up as a topic of conversation. Right. And so they say like, I see you're doing this for longevity, but you know, like I've seen so many examples where people put money in, and you lose the founder. Like they're off. And everyone's high and dry. And so they were telling me that they put into deal docs that they can't do this for the duration of the company. And so it is a thing. And you know, I
[20:16] I have nothing to say about it other than I know it happens. Um, also I would say that most people in the tech world that I'm familiar with, again, they've done this in retreat centers or in social environments. It's not quantified. It's not set and setting. It's So it's a different thing. But I will say like, you know, I I guess me as a person, what I'm trying to focus on, I came back even more motivated to do what I'm doing now. Uh, I don't have a desire to go off
[20:46] in the woods, you know, and like and live that kind of life. It It It emboldened me to work on these things, but no question about it, you you do have a dramatic shift in perspective. And it's it's very hard to get away from >> a very important philosophical question. Who am I? Yes. If I'm defined by my experiences, it roughly equates to my neurons are wired in a way that's a consequence of my experiences. And if I go in and take a drug and in a
[21:17] few hours rewire all my neurons, am I the same person? What makes Brian Brian? You can maybe recall some memories of Brian prior to taking the psychedelic, but Brian as a person has been rewired. Are you a different person now? And what does that say about Are we ever a persistent person? >> Yeah. Right? Yeah. Your question is spot on. Probably the most dramatic reconstruction of your 60 plus trillion cells than anything you can do in life.
[21:48] Yeah, like maybe like a near-death experience, you know, would would maybe uh be close, but it's a dramatic re-wiring of you as a as a human. Your values can change, too. That's right. And you could judge the values pre and post, right? You could judge values ascribed to you by a religion or perhaps values ascribed to you by responsibility to family members, children, spouses, partners, what have you. You abandon them after you go through this change. So your values have changed. Is it right or wrong? >> That's right. I think it's another important question that comes out of all
[22:19] this. >> And like you know, like you now think about that That's within the frame where the world changes at a certain speed. Now you take the world where it's changing faster. So we now know that it's hard to predict what's going to happen 2 weeks from now or a month, right? Like things are changing very quickly. And so now you come up with this practical question, can humans change fast enough in the world where AI is the dominant engine of innovation? And so in that case, like you may want
[22:49] psychedelics as your ally to say, as a human I'm struggling to like move with the change. Yeah. And so there there's potentially a where it it flips from a liability to an asset where like now I do want that restructure changing, even though you have some tail risk of like maybe my priorities will shift. >> you have profound what I would call psycho-flexibility. And I think most people don't. They have either a disinterest in changing who they are overnight or they're fearful of the the ramifications or the experience. And
[23:21] that they wouldn't go through it. How far would you take it? Would you wire yourself up to a neuralink or neural enhancement device that would give you the ability to have information on demand and maybe change your personality and capacity as a human through an implant? Would you consider doing something like that? >> Yes. You would. Would you consider a transgenic system where you basically take a plasmid, which would then express a set of proteins in your body and change uh gene expression profiles and cells in your body and basically could rewire you as a different person? Yes.
[23:51] Yes. Is there a limit to what you would try? >> No. Interesting. Where do you think that comes from? I think I I find it to be the most exciting configuration of life. Uh, the ability to play on the frontier. Uh, novelty and expedition and challenge. That's really my Did you always have it or are you responding to childhood suppression of those I mean it's it's probably it's probably an overcompensation of of trauma response, like most things are. And so, you know, as a child I lived in a very structured
[24:22] religious environment where things were cemented. Like here's the story, here's the plan, here's what you do and what you don't do. Yeah. And so yeah, maybe it's probably just I'm now a flipped in the opposite. Yeah. And so I mean that's like probably true that I really I don't trust my internal generation of reality. You know, I know I'm always making things up. I've got 188 chronic biases, like all humans do. So I'm just I'm generally suspicious of all things all time, and I don't take myself very seriously. So I just find the the
[24:52] frontier play space to be like Right now, I mean, you know, what you're doing in building companies, like you just open up a a toolkit and say like, what can I build? And how do I modify? And so I agree with you. I do have a a strong proclivity towards open display. Do you find that you've been challenged in maintaining, I would call it external responsibility as you explore and enhance yourself so much? Do you give up the responsibility to others around you who maybe are dependent on you or or in need of you? Yeah. I have three kids. And so um
[25:22] I do think about them a lot. And I being a father is a really important thing to me, and it's an important part of my identity. And so that has not changed. So I've never uh vacillated on that or changed my disposition towards that. Uh for those around me, I guess fortunately I have a a social group that just says, go and play. There's There's really no one in my life that tries to claw me back. There's no Velcro. Yeah. It's just all encouraging. And so that I guess I feel very fortunate that everyone around me and
[25:53] they're willing to take the risks. I mean, this is you know, when I sat down for 5-MeO, I mean my my partner Kate, like she's got a ton of risk. Like what if it goes poorly? What if I change my perspective? What if something bad happens? So Well, one could make an argument that taking that degree of risk where something could have gone wrong, the people around you are enabling versus Yeah. being supportive, right? That's right. That's right. >> yeah, that's That's a consequence, but let's shift topics to other uh modalities for longevity. Yeah. What
[26:23] else is on the horizon? So you've had this profound set of experiences with psychedelics. You've documented in a very extraordinary and exquisite fashion all of the other things that you've been doing with interventions. Are there other things that are on the horizon that you're either excited about or that you're considering yourself? Yeah, I mean, two of the ones that we've spoken about, cell therapy and gene therapy. >> Yeah. Yeah. They they're all in the pipeline. Uh so they're not ready yet. We've We've knocked out all the stuff you can do today. Like we've gone through it all, done it all. Um the next gen therapies
[26:54] are just not there yet. So we're looking at mitochondrial rejuvenation. I think that's incredible. I think mitochondrial augmentation therapy. And there was a paper I saw where in order to get the mitochondria in the cell, they coated the mitochondria in effectively a red blood cell envelope, >> Yep. which made it more transportable into cells and less uh attacked by the immune system. >> Which is incredible. And I I'm a big big big believer in this this this course of therapy. I think it's going to be a whole therapeutic modality that no one has even recognized. >> We have our first uh mitochondrial
[27:24] therapy lined up. So How are you going to do it? You're You're like 99.9%. You need someone who's like 48.7% >> [laughter] >> to try the mitochondrial particularly like, you know, I think they tried it in Parkinson's patients, Alzheimer's patients. That's where you can really see profound shifts in in certain metrics. For you, it's like 99.9 to what? Like >> Yeah, yeah. You know, I had the mitochondria, you know, of a 48-year-old. Right? So like, what what if I What if I could >> Yes. You could go to your sibling's child because the the mitochondria is
[27:54] passed maternally cuz it's in the it's in the egg cell. So it's the mother's mitochondria. >> Right. If you have a a sister who has a kid, they're going to have very young mitochondria. You can take a little blood sample and then grow their mitochondria extensively and use that as a biological match to you. >> This is a perfect extension. I've had a blood boy as a son. Yeah. So now I'm just going to go to the extended family and be like, guys, it's a it's a family project. Yeah, family project. Yeah, yeah, exactly. Well, that one's super interesting. And
[28:24] then >> have one that we're doing I've I'm now building >> Sorry, are you going to do your own mitochondrial transplantation? You're going to build a bioreactor or are you using working with a one of the third parties that Yeah, third company, yeah. So I'll I'll get I'll do a blood draw in the next week or two. They'll spin up. And then we'll do it. Yeah, I'll do it. Yeah. So you're going to get your mitochondria, which have some you know, the the problem with mitochondria, as you know, is mitochondrial DNA degradation over time, right? It accelerates for certain people, but that way if you go back to a young person, you have young mitochondria. But then you're going to multiply yours
[28:54] out. Yes. And probably select a little bit or for healthier ones. Right. Okay. And then put it back in. It's very I mean, it's exploratory. We don't know. We're one of the first. They're They're in phase two now. Do you sprint? Yeah, I do. So you could probably score if you did it intramuscular like mitochondrial therapy, you could sprint see your score. That's a great idea. Yeah, thank you. Uh that would be a great way to measure it from a rather than just a basic biomarker perspective. Be really interesting to see. Yeah. Sprinting is one of the most underappreciated longevity therapies. Yeah, I I don't do
[29:24] it. Oh, man. >> I've got the the age of a 74-year-old uh roughly. >> [laughter] >> I am uh I'm definitely not keeping track with you. Would you consider or have you looked at any plasmids where you take a gene as DNA, put it in your body, and then that gene makes a protein in your body that that does something? Like the one we were looking at in the FoxO3 expression. Yeah, exactly. So the mesenchymal stem cells it packaged up with the Foxo 3 delivery. Um yeah, that showed that over 50% of tissues getting that rejuvenation.
[29:54] >> It's unbelievable. >> Unbelievable. It's like the It's the best demonstration in the entire world. >> for tissue regeneration. Like as a particular application set, tissue regeneration using that sort of system seems like a no-brainer. Like, yeah. >> It's safe, right? It's like it's Yeah, so I reached out to that Chinese professor. I'm really interested in seeing it replicating. I would love >> out to the Chinese professor? >> Yeah. That's awesome. [laughter] >> Yeah. We sent that paper Yeah, yeah, yeah, yeah, yeah, yeah. That's awesome. So, I Yeah. >> Awesome. Yeah. Good. Uh so, we I'd love to do that. Um I'd love to actually
[30:24] build it ourselves. Yeah, but that's like a 2-year project. So, um Hey, I can help. Make it faster. >> That's true. Yeah. Actually, that's true. AI as a project manager for these sorts of programs is You know, that's true. We We spoke about this 6 months ago. Yeah. >> they're so different. So different now, 6 months later, in terms of standing it up. Um so, that one's cool. So, I think that's a good good option. Then also, I'm doing uh Bryan Johnson organoids. So, uh we took my iPS iPSCs. We now have them >> Induced pluripotent stem cells. So, you took your cells, turned them into stem cells. Yep. Yeah. So, now we're doing in
[30:54] dish. So, now we have like a Bryan Johnson heart, liver, lungs. And now we're going to try molecules on me and in dish. >> have a plot So, so let me just walk the audience through this. So, you take cells off of your skin or something blood, and then you put these Yamanaka factor proteins on those cells, causes those cells to become stem cells, which means they can then turn into any other cell. And then you put other proteins on them to turn them into a heart cell or a eye cell or or what have you. And now you've got a store of these tissue-specific Bryan Johnson cells >> Yes. that you then use for Like, you can
[31:25] say, "Okay, what if you give Bryan Johnson blank you know, drug? What is What happens? Is it good? Is it bad? What are the side effects? What are the complications? >> dish, you put the drug in there. See what happens. >> Yeah. Okay. >> just like you can simulate all these experiments. So, now you you get the advantage of time, of acceleration, of like what to take, why, what dose. That's awesome. Uh what combinatorial things to consider. Yeah. >> we we have the organoids stood up. We haven't done our first test yet. Yeah. So, that's interesting because now I have to do this old-school methodology, like put it in my body, wait to see what happens. Is it good? Is it bad? What you
[31:57] know, how does it affect everything else? >> Yeah, totally. That's a good one. But let me I don't know, we'll see. It's It's cool in concept. I mean, TBD if it actually works. So, we'll see. Have you tracked any of the alternative Yamanaka factors, their factor discovery work that's going on? And do you think there's anything worth testing at this stage? Yeah, I'm a an investor in NewLimit. So, I've talked to them about the where they're at and Blake and Bryan's company. They've done I mean, they've made remarkable progress. They they figured out how to computationally solve the discovery process. Yeah. And
[32:27] so, I they um they're much faster than they initially thought. And so, that's very encouraging. >> the big challenge with the Yamanaka factors is always dosing. If you overdose a cell, a one cell, that cell can become a cancer cell and take off as a tumor. >> Yeah. So, the sensitivity that you need to have to get the right number of the factors, which is a protein, into the cell needs to be Yeah. perfectly tuned. Yeah. So, I have a theory that this will end up being solved by cellular switches Hmm. that will end up putting machinery into the cells that can turn on or off
[32:58] the protein synthesis at the right dosing based on the measurement of gene expression in the cell. That's my theory on where this will end up. >> of sense. Any other control mechanism will be inadequate. >> That's right. >> The feedback loop just All you need is one error and you're you're you're in trouble. Yeah. But it is it is the most profound, I think, technology that humanity's dealing with today besides AI. We're not quite there with fusion, which I would argue is probably a distant third, but it is very powerful if possible. >> again, in the future, like I think we'll look back and we'll see GLP-1s as the first big drop. Yeah.
[33:28] >> I'm like, "What? I can just inject myself and like it solves hunger and you know, and then the second will probably be something like NewLimit or one of these Foxo one of these plasma-based Foxo 3 therapies where it will show real life like dramatic changes. And then humanity will shift as like uh longevity being a vision of sci-fi, you know, rich people pursuit to like something that is truly Yeah, I mean, go back to like the conversation on on the temptation towards socialism. Right? Like, if if you can feel robust in your ability to
[34:00] pursue life and be healthy and vibrant and uh in control, I think these things could have dramatic changes in society, not just in health, but like Well, any form of abundance, whether it's abundance in food, in energy, in housing, in mobility, in life the more abundant people get, the happier they are. And the more you're improving abundance in the world, the the better we are going to live as a group of people together on planet Earth. >> Exactly. The happier we will all be with each other. But I think like honestly, like a lot of the the the
[34:30] >> External conflict only comes from internal unhappiness. 100%. And so, if you look at the general malaise of like American society, like no wonder uh things are shitty, right? Like, you've got meta 84% of people have metabolic disorder. Over 40% of people are obese. Like, we're just in really poor health. Nobody's sleeping. Everyone's on their phone. Like, mental health issues. Like, no wonder you have the proclivity towards these kinds of outcomes. Like, so if you could get the health in check, it changes the psychological disposition of you, your community, your country. Like, you have much more of a can-do attitude. Like, I
[35:01] can take on the world and I can do hard things. But when you're not feeling well, like it's just everything is just so much harder. >> Yeah, 100%. And so, in light of all of these new therapeutic modalities and these new opportunities that seem to be biologically proven and have these profound effects, why continue to tinker with psychedelics? Like, are they as profound or are they a complement or like how do you think about fitting all of this portfolio of things that you're looking at together? >> Yeah. I mean, I guess the question is I forget on the Foxo 3 study. I don't know if they saw brain rejuvenation. >> I did not see that. And I don't I don't
[35:32] remember. I mean, it is a very complicated organ. Yeah, exactly. And it's insane. Like, you know, you can grow muscle tissue back and you can grow skin tissue back and it's kind of like, "Okay, I grew a little like Like, if you grow the the the neurons back maybe in the wrong way like we don't know Yeah. because it's never been done before. >> Yeah. So, understanding the consequence of neuro regeneration is like So, I wonder like if the role it might play. Like, you know, maybe psilocybin and 5-MeO won't be
[36:03] um you know, meaningful for like basic functions of the body. But maybe it's the the outperformer in youthfulness of your of your disposition towards reality. Like, one thing I'm I'm apprehensive about is you know, I'm 48. And so, as you start climbing to your 50s, 60s, you do really narrow. Like, your ambition goes from I can do anything to start, you know, narrowing down further and further. And
[36:33] I worry about using losing a youthful disposition of a can-do attitude, of anything is possible. Totally. And maybe that's the role of psychedelics is you just get a wash of like the snapback of like, I can and I can bounce. That's definitely been the case for me. So, I think they do probably play a really important role of like they're probably a set of things that for certain people that will um It It's basically like I mean, I felt like it was like 30, 40 years of
[37:06] psychological rejuvenation. Like, you know, it's like to transform me back to a childlike state, that is insane. I don't get that from the sauna or from eating well or from sleeping well. Like, I'm still >> Right. So, it's They're just unique. Yeah, amazing. Well, listen, I'm going to go drink alcohol and eat carbs and stay out late. I don't know, what are you going to do? I'm going to go to bed on time and do my wind-down routine. Yeah, you do you. But but you do you as well. Enjoy [laughter] it. I appreciate it. This has been great. Bryan Johnson, thank you. >> Yeah, that was awesome. That was great.
[37:36] I'm going all in. I'm going all [music] in.